Lauren B. Krupp, MD: The treatment for MS [multiple sclerosis] has evolved in a very fascinating way, particularly in the pediatric age group. Years ago, there were no treatments for MS. That was before 1993. There was a tendency for pediatricians and pediatric neurologists to call anything that was inflammatory and demyelinating in childhood a condition called ADEM [acute disseminated encephalomyelitis]. That was because ADEM was a self-limited condition and was a lot less frightening than something like multiple sclerosis, which is a chronic illness. But when therapies became available for MS, which was in the 1990s, it soon became apparent that these therapies worked best if you started them early. So early treatment means an accurate diagnosis as soon as possible.

The initial wave of therapies were all injections. We had interferons. We had interferons that were given subcutaneously, intramuscularly. Some were given every other day, others were given 3 times a week, and 1 of them was given once a week. The other medication that was given daily, initially, and then 3 times a week later was glatiramer acetate. These are all different medications that modify the immune system in a way that’s favorable for the person who has MS. That was really all there was.

Later, there was some work with a chemotherapy agent called mitoxantrone. However, that was pretty toxic and people have really shied away from using that because of cardiotoxicity and other challenges. In the mid-2000s, the first infusion therapy became available, in the United States at least, for MS, and that was natalizumab. Both in Europe and in the United States, some clinicians would use natalizumab. But more often, clinicians would use the injectable therapies. The reason for that is although natalizumab, or Tysabri, is an extremely effective medication, it has 1 really serious risk factor. Some people are vulnerable to getting a brain infection known as PML [progressive multifocal leukoencephalopathy]. Since nobody wanted a child to have that, there was a tendency to shy away from natalizumab.

A major breakthrough in therapy occurred in 2018 with the publication of the efficacy of the drug fingolimod, an oral medication, in pediatric MS. That was the first FDA-approved medication for pediatric MS. Up until that time, clinicians would use these other MS drugs approved for adults in what’s called an off-labeled fashion to provide them or prescribe them for children, which made a lot of sense because it’s the same disease. Whether you’re age 15, or 35, or 55, if you have MS it’s an autoimmune disease, and certain characteristics will respond to these therapies.

What we found with the clinical trial that was published in the New England Journal of Medicine was that children—the study only looked at those 10 to 17 years of age, so there wasn’t any real work on the youngest kids—respond really well to this medication. In that study, it was compared to one of the injectable therapies where that medication, the injectable therapy, did not work very well. In fact, it worked pretty poorly. What that showed is that the first-line therapies, in many cases, are just not sufficient. In my own experience, before we had the oral therapy and before we had the infusion therapies, what would happen is you’d start one of the injectable therapies and it would work for a little while. But then, the child would have another relapse or MS attack with new neurological problems.

So then you would go to one of the other injectable therapies, hoping that would be a little bit better for this child. A meta-analysis is when you take all of the published data and compare across studies to see what works and what doesn’t. This hasn’t been done for pediatric MS, but it has been done for adults. There are more similarities between the injectables than there are differences. For example, the medication glatiramer acetate doesn’t show that much of a difference when compared head-to-head with one of the interferons. So if you’re failing one, there’s a good chance you’re going to fail the other, too. And so we would be in this very frustrating situation.

Now we have more effective therapies. Fingolimod is a pill. It’s very effective. We have infusion therapies. Natalizumab, for the right patient, is a beautiful therapy. And because I believe in using medicines that are effective in adults in children, we have other infusions, such as ocrelizumab. And an off-label treatment is rituximab. All of these mABs are monoclonal antibodies, and they’re sort of like a sniper because they’re targeting a very specific molecule and blocking that molecule with the effect of either preventing the activated immune cells from getting into the central nervous system or taking out of the circulation those immune cells that are causing problems in MS. By being targeted in that way, you can hope that the adverse effect profile will be more manageable. But these medicines do require a fair bit of monitoring.